{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:29:12Z","timestamp":1791217752379,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T00:00:00Z","timestamp":1379548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of Education, Science, and Culture of Japan","award":["21592634"],"award-info":[{"award-number":["21592634"]}]},{"name":"Ministry of Education, Science, and Culture of Japan","award":["23792487"],"award-info":[{"award-number":["23792487"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2014,8]]},"abstract":"\n Objective and Background<\/jats:title>\n \n Periodontitis is an inflammatory disorder of the supporting tissue of teeth, which is composed of gingival soft tissue, cementum covering the tooth root, alveolar bone and periodontal ligament. The receptor activator of nuclear factor kappa B ligand (\n RANKL<\/jats:styled-content>\n ) is known to be an essential factor for osteoclastogenesis. Recent clinical studies indicate that levels of\n RANKL<\/jats:styled-content>\n in the gingival crevicular fluid are increased while levels of its decoy receptor, osteoprotegerin (\n OPG<\/jats:styled-content>\n ), are decreased in patients with periodontitis. Although the gingival sulcus is composed of gingival tissue,\n RANKL<\/jats:styled-content>\n and\n OPG<\/jats:styled-content>\n expression in gingival epithelial cells is not fully understood. The aim of this study is to investigate the expression of\n RANKL<\/jats:styled-content>\n and\n OPG<\/jats:styled-content>\n in gingival tissue and which factors regulate\n RANKL<\/jats:styled-content>\n expression in gingival epithelial cells.\n <\/jats:p>\n <\/jats:sec>\n \n Material and Methods<\/jats:title>\n \n Reverse transcriptase polymerase chain reaction analysis, western blotting and immunohistochemistry were performed to confirm\n RANKL<\/jats:styled-content>\n and\n OPG<\/jats:styled-content>\n expression in gingival epithelial cells (\n GEC<\/jats:styled-content>\n s) and in gingival tissue. Immunostaining was also examined to confirm tumor necrosis factor (\n TNF<\/jats:styled-content>\n )\u2010\u03b1 and\n TNF<\/jats:styled-content>\n receptor type 1 (\n TNFR<\/jats:styled-content>\n 1) expression in gingival tissue. Ca9\u201022 cells, a human gingival epithelial cell line and human primary\n GEC<\/jats:styled-content>\n s were treated with\n TNF<\/jats:styled-content>\n \u2010\u03b1. Ca9\u201022 cells were treated by antibodies against\n TNF<\/jats:styled-content>\n receptors, an inhibitor and an activator of protein kinase A (\n PKA<\/jats:styled-content>\n ) signaling and inhibitors of p38, Erk and\n NF<\/jats:styled-content>\n \u2010\u03baB signaling to examine\n TNF<\/jats:styled-content>\n \u2010\u03b1\u2010\n RANKL<\/jats:styled-content>\n signaling pathways.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n RANKL\n mRNA<\/jats:styled-content>\n and protein were expressed in GECs. Immunohistochemistry also showed RANKL expression in gingival tissue. On the other hand, the reverse transcriptase polymerase chain reaction and immunohistochemistry assay showed that GECs did not express OPG. In addition, TNF\u2010\u03b1 and TNFR1 proteins were expressed in junctional epithelium. TNF\u2010\u03b1 increased RANKL expression in GECs. TNF\u2010\u03b1\u2010induced RANKL expression was inhibited by an antibody against TNFR1 and an inhibitor of PKA signaling. Surprisingly, forskolin, a PKA activator, increased TNF\u2010\u03b1\u2010induced RANKL expression.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n RANKL<\/jats:styled-content>\n ,\n TNF<\/jats:styled-content>\n and\n TNFR<\/jats:styled-content>\n 1 were coexpressed in junctional epithelium of gingival tissue.\n TNF<\/jats:styled-content>\n \u2010\u03b1 induced\n RANKL<\/jats:styled-content>\n expression via\n TNFR<\/jats:styled-content>\n 1 and\n PKA<\/jats:styled-content>\n signaling in\n GEC<\/jats:styled-content>\n s of junctional epithelium.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jre.12131","type":"journal-article","created":{"date-parts":[[2013,10,8]],"date-time":"2013-10-08T12:22:32Z","timestamp":1381234952000},"page":"508-517","source":"Crossref","is-referenced-by-count":67,"title":["Tumor necrosis factor\u2010\u03b1 enhances\n RANKL<\/scp>\n expression in gingival epithelial cells via protein kinase\n A<\/scp>\n signaling"],"prefix":"10.1111","volume":"49","author":[{"given":"R.","family":"Fujihara","sequence":"first","affiliation":[{"name":"Department of Periodontology Showa University School of Dentistry Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Usui","sequence":"additional","affiliation":[{"name":"Department of Periodontology Showa University School of Dentistry Tokyo Japan"},{"name":"Division of Periodontology Departmetnt of Cariology and Periodontology Kyushu Dental University Kitakyushu City Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology and Diagnosis Showa University School of Dentistry Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Nishii","sequence":"additional","affiliation":[{"name":"Department of Periodontology Showa University School of Dentistry Tokyo Japan"},{"name":"Department of Oral Pathology and Diagnosis Showa University School of Dentistry Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Tsukamoto","sequence":"additional","affiliation":[{"name":"Department of Periodontology Showa University School of Dentistry Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Okamatsu","sequence":"additional","affiliation":[{"name":"Dental Clinic Showa University Medical Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Saitama Medical University Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Asou","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Tokyo Medical and Dental University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Division of Periodontology Departmetnt of Cariology and Periodontology Kyushu Dental University Kitakyushu City Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Periodontology Showa University School of Dentistry Tokyo 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